【作者】 陈飞宇；

【导师】 唐利立；

【作者基本信息】 中南大学 ， 外科学， 2008， 硕士

【摘要】 目的:初步研究S-TK1含量在乳腺癌患者、健康体检人群及乳腺良性肿瘤患者中的差别;探讨乳腺癌患者S-TK1的含量与分期、肿块大小、组织学分级、ER、PR及C-erbB-2之间的关系;探索乳腺癌患者新辅助化疗前后S-TK1含量的变化对预测新辅助化疗疗效的意义。方法:选取2007年7月到2007年12月中南大学湘雅医院乳腺科就诊的女性乳腺疾病患者60例,其中经巴德针穿刺病理证实的乳腺癌患者共40例(A组),均行新辅助化疗2～4个周期,另外20例为经手术证实的乳腺良性肿瘤患者(B组)。A组患者新辅助化疗前(A1)及化疗两个周期结束后(A2)各留取一份血清标本,B组患者术前留取血清标本。从2007年10月中南大学湘雅医院健康体检者中随机选取女性20例(C组),留取血清标本。均保存于-20℃冰箱备用。所有血清标本均采用化学发光点印迹法检测其S-TK1的含量。所有统计分析采用SPSS11.5 for windows统计软件完成,每两组之间的差别采用两个独立样本的t检验或是配对t检验,各个因素的半定量与S-TK1值(平分为三个等级)之间有无相互关系,采用Spearman等级相关性分析。结果:(1)、乳腺癌患者新辅助化疗前(A1组)S-TK1的含量为17.98±10.20pmol/L,乳腺良性肿瘤患者(B组)S-TK1的含量为1.50±1.02 pmol/L,健康体检者(C组)S-TK1的含量为0.88±0.45pmol/L。A1组S-TKl的含量明显高于B组和C组,差别有统计学意义,P值均<0.001;B组S-TK1的含量高于C组,也有显著性差别(P=0.017)。A1组Ⅲ期乳腺癌患者S-TK1的含量高于Ⅱ期患者,差别有统计学意义(P=0.018)。(2)、S-TK1的含量与组织学分级、C-erbB-2及肿块大小呈正相关,其相关系数分别为r=0.596、0.324、0.397,对应的P值为P<0.001、=0.042、=0.011;而ER与S-TK1的含量呈负相关,其r=-0.391,P=0.013;PR与S-TK1的含量无相关性,P=0.395,r=-0.138。(3)、乳腺癌患者行两个周期新辅助化疗后(A2组)S-TK1的含量为9.24±9.79 pmol/L,明显低于新辅助化疗前(A1组)S-TK1的含量,差别有统计学意义(P<0.001)。总体临床客观反应(OR)组与无反应(NR)组新辅助化疗前后S-TK1含量减少的百分比分别为65.71%±20.25%,17.20%±42.20%,OR组明显高于NR组,差别有统计学意义(P<0.001),且Ⅱ期和Ⅲ期乳腺癌患者临床客观反应(OR)组S-TK1含量减少的百分比均明显高于无反应(NR)组,差别都具有统计学意义(P=0.013、0.007)。OR组与NR组新辅助化疗前S-TK1的含量两组之间差别无统计学意义(P=0.378)。结论:(1)、S-TK1的含量在乳腺癌患者中明显升高,而在乳腺良性肿瘤患者和健康人群中维持较低水平,且S-TK1在乳腺良性肿瘤患者中的含量高于健康人群,S-TKl在Ⅲ期乳腺癌患者中的含量明显高于Ⅱ期乳腺癌患者,提示S-TK1可以作为乳腺癌诊断及在健康人群筛查的一个较好的指标。(2)、乳腺癌患者中S-TK1的含量与组织学分级、C-erbB-2及肿块大小呈正相关,而与ER呈负相关,说明S-TK1的含量随肿瘤的恶性程度升高而增高。(3)、乳腺癌患者新辅助化疗后S-TK1的含量比化疗前明显降低,并且新辅助化疗后,无论总体还是期内(Ⅱ期或Ⅲ期)临床客观反应(CR+PR)组S-TK1含量减少的百分比均明显高于无反应(SD+PD)组,提示S-TK1的含量可以做为观察乳腺癌新辅助化疗疗效的指标,其与长期生存率的关系在进一步随访研究中。更多还原

【Abstract】 Objective:To study the difference of S-TK1 level among patients with breast cancer,patients with benign breast tumor and healthy volunteers;To investigate the correlation between S-TK1 level and staging,the size of tumor,grade,ER,PR or C-erbB-2 in patients with breast cancer;To explore the significance of the changes of S-TK1 level in patients with breast cancer before and after neoadjuvant chemotherapy in predicting the effect of neoadjuvant chemotherapy.Methods:60 cases of female patients with breast disease were selected from the Department of Breast Surgery in Xiang-Ya Hospital of Central South University,from 2007 July to 2007 December.Among the total,40 cases were confirmed as breast cancer in pathology by BIRD needle biopsy(group A),each of which were under 2～4 cycles neoadjuvant chemotherapy.The other 20 cases were patients with breast benign tumor and were confirmed by surgery(group B).In group A, serum samples were collected before(group A1)and after 2 cycles(group A2)neoadjuvant chemotherapy,and in group B,the serum samples were collected before surgery.20 cases of female healthy volunteers were randomly selected from healthy examination in Xiang-Ya Hospital in 2007 october(group C),each of whose serum samples were collected. All serum sample were stored in—20℃.All the serum samples were detected S-TK1 level by enhanced chemiluminescence(ECL)dot blot assay.SPSS 11.5 software was used to analyse the data.The difference between every two groups was analysed by two independent-samples t test or paired-samples t test.The correlations between S-TK1 level(which were equally divided into 3 ranks)and the semiquantitative of each factor were performed using Spearman rank correlation.Results:(1)The concentration of S-TK1 in patients with breast cancer before neoadjuvant chemotherapy(group A1)was 17.98±10.20pmol/L,in patients with benign breast tumor(group B)was 1.50±1.02 pmol/L and in healthy volunteers(group C)was 0.88±0.45 pmol/L.There was significant difference between group A1 and group B or group C(P＜0.001,P＜0.001), and between group B and group C(P=0.017).Also in group A1 the concentration of S-TK1 of stagingⅢwas significantly higher than stagingⅡ(P=0.018).(2)The concentration of S-TK1 was found to have a positive correlation with grade,C-erbB-2 and the size of tumor(r=0.596、0.324、0.397,P＜0.001、P=0.042、P=0.011).There was a negative correlation between ER and the concentration of S-TK1(r=-0.391,P=0.013).But it was not found the concentration of S-TK1 had correlation with PR(P= 0.395,r=-0.138).(3)The concentration of S-TK1 in patients with breast cancer after two cycles neoadjuvant chemotherapy(Group A2)was 9.24±9.79 pmol/L,and it was significantly lower than that in patients before neoadjuvant chemotherapy(Group A1)(P＜0.001).The decreased percentage of S-TK1 concentration after and before neoadjuvant chemotherapy in group of objective clicinal response(OR)was 65.71%±20.25%and in group of no response(NR)was 17.20%±42.20%.And there was a significant difference between these two groups(P＜0.001). Otherwise in stagingⅡor in stagingⅢthe decreased percentage of S-TK1 concentration after and before neoadjuvant chemotherapy of Group OR is significantly higher than that of Group NR(P=0.013、0.007).But the concentration of S-TK1 before neoadjuvant chemotherapy was not found significant difference between group OR and NR(P=0.378).Conelutions:(1)The concentration of S-TK1 was significantly high in patients with breast cancer,but kept low in patients with benign breast tumor and healthy people.And it was significantly higher in patients with benign breast tunor than in healthy people.Also in patients with breast cancer it was higher in stagingⅢthan in stagingⅡ.So S-TK1 can be a good marker for diagnosing breast cancer and for screening breast cancer in healthy people.(2)In breast cancer the concentration of S-TK1 had a positive correlation with grade,the size of tumor and C-erbB-2,while had a negative correlation with ER.So,with the tumor becoming more malignant the concentration of S-TK1 rose.(3)The concentration of S-TK1 was significantly lower in patients with breast cancer after neoadjuvant chemothyrapy than before neoadjuvant chemotherapy.And in total or in each staging(stagingⅡor stagingⅢ)the decreased percentage of S-TK1 concentration was significantly higher in group of objective clicinal response(CR+PR)than in group of no response(SD+PD).So the concentration of S-TK1 can be a marker for observing the effect of neoadjuvant chemotherapy.And the relation between the concentration of S-TK1 and long term survival is being studied in the further follow-up.更多还原